Ceftiofur, a semisynthetic cephalosporin, is a broad-spectrum antibiotic against both Gram-positive and Gram-negative bacteria including beta-lactamase-producing bacterial strains and anaerobes. Its antibacterial activity results from the inhibition of mucopeptide synthesis in the cell wall in a similar fashion to other cephalosporins. Ceftiofur is used in the treatment of respiratory infections in cattle and pigs. The chemical designation is [6R-[6a,7b(z)]]-7-[[(2-amino-4-thiazolyl) (methoxyimino)acetyl]amino]-3-[[2-furanylcarbonyl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid. The sodium and hydrochloride salts are administered intramuscularly and intravenously.
Ceftiofur is first disclosed in U.S. Pat. No. 4,464,367, which also discloses a process for preparing Ceftiofur and its sodium salt.
There are various literature methods reported for the preparation of cephalosporin compounds like Ceftiofur which are summarized below:
U.S. Pat. No. 5,109,131 describes a process in which 4-halo-2-methoxyimino-3-oxobutyric acid, is reacted with cephem moiety as per the scheme depicted below:
wherein R1 stands for a C1-4 alkyl group optionally substituted with carboxyl or a C1-4 alkoxy-carbonyl group, R2 stands for a halogen atom, R3 stands for hydrogen atom or a standard cephalosporin substituent which includes Ceftiofur also, and R4 stands for hydrogen atom or a group which can be converted to hydrogen
U.S. Pat. No. 4,298,529 describes a similar process as depicted in U.S. Pat. No. 5,109,131, according to this patent the cephem compound of formula may be used as such or as a silyl derivative (column 12, lines 20-23 of U.S. Pat. No. 4,298,529).

CA 1,146,165, also discloses a similar approach for the preparation of cephalosporin compounds.
EP 0030294 discloses a process for the preparation of compound of cephalosporin antibiotic as given in scheme 1:

wherein R represents hydrogen atom or a readily hydrolysable ester group and X represents one of the groups
GB 2012276 describes 7-(4-halogeno-3-oxo-2-alkoxyiminobutyrylamino) cephalosporin derivative of the formula (XIII)
wherein X represents a halogen atom, R3 represents —CH2R5 (R5 is hydrogen atom or the residue of a nucleophilic compound), a halogen atom, an alkoxyl group, thiol group, amino group etc., —COOR4 represents a carboxylic group which may be esterified, and R6 represents an alkyl group and also a process for preparing a 7-[2-(2-aminothiazol-4-yl)-2-(syn)-alkoxyiminoacetamido] cephalosporin derivatives of the formula (XIV)

U.S. Pat. No. 6,552,186 relates to the preparation of ceftriaxone and cefotaxime also claims a process for the preparation of number of cephalosporin antibiotic including Ceftiofur using similar approach disclosed in prior art. As cited by US publication No. 2005/0059820, this patent itself obvious and anticipated over prior art. Moreover this patent utilizes two phase solvent system, the one of the disadvantages with the two phase solvent system in cyclization with thiourea stage is that the reaction takes more times to completion or many times reaction will not complete and leaves 7 to 15% starting material; also yield less pure API.
Thus the above literature reports like CA 1,146,165, U.S. Pat. No. 4,298,529 and U.S. Pat. No. 5,109,131 (which are published after the grant of U.S. Pat. No. 4,464,367, where Ceftiofur is first disclosed) and U.S. Pat. No. 6,552,186 pertaining towards the preparation of Cephalosporin antibiotics suggests and teaches the following general scheme for the preparation of Ceftiofur of formula (I):

Though the literature pertains to cephalosporin chemistry, which suggests or motivates the above general process, U.S. Pat. No. 6,458,949 claims a similar process for preparing Ceftiofur. According to this patent the purity of final Ceftiofur depends on the isolation of compound of formula (C). This patent also acknowledges that cyclization of compound of formula (C) in-situ with thiourea in the presence base yield impure Ceftiofur and further purifications are difficult, time consuming and do not result in a product of good quality. Also this patent claims the compound of formula (C) though it is obvious over cephalosporin chemistry.
In our continued research we have identified a process for the preparation of Ceftiofur, in which even though the compound of formula (C) is not isolated, yield Ceftiofur in highly pure form, whereby avoiding the time consuming filtration step and makes overall process commercially viable and economical. None of the prior art suggest or event motivates the present invention.